Our aim is to understand the structure-function relationship of modified nucleosides in nucleic acids, tRNA, rRNA and mRNA. Our objective is to establish, by x-ray diffraction techniques, the details of the stereochemistry of modified nucleosides and mRNA caps. We will investigate the details of the stereochemistry of codon-anticodon interaction, the reading of the genetic code and the roles played by modified nucleosides. We will develop stereochemical criteria that will be of some help in developing a rational chemotherapy program involving modified nucleosides, cytokinins and protein synthesis inhibitors that are analogs of mRNA caps and the "two-five A's". We will investigate the intercalation of water and ions between nucleic acid bases and the consequences of such intercalation in nucleic acid structure and function.